SPECIFIC AIM:Identify messenger RNA and microRNA gene expression profiles that are uniquely associated with prostate cancer in African-American males.Our research is aimed to identify genetic factors, and interactions between genes and the environment, that contribute to the high prostate cancer incidence and mortality rates among African-American men. There is an immediate need to prevent the progression of the clinically localized disease by increasing the understanding of the basic biology of prostate cancer. The propensity for disease progression is different for African-Americans and Caucasians. A critical challenge is to develop methods that distinguish indolent cancers from those that are potentially lethal. The application of gene expression profiling to study prostate cancer has resulted in significant successes, including the identification of novel clinical markers that improve tumor classification and the prediction of outcome. Although these investigations have shown that gene expression profiles can identify recurrence-related molecular profiles, there is no such study in the literature that has attempted to identify the genes and pathways with relevance to the etiology and aggressive behavior of prostate cancer in African-Americans. There is strong evidence that gene products of both tumor and stromal cells drive tumor progression. There are multiple and significant interactions between stroma and cancer cells in prostate cancer. Still, the expression profile of the stroma adjacent to prostate tumors has not yet been studied. Thus, we will establish messenger RNA (mRNA) expression profiles for both tumor cells and the stroma, and compare them between the two race/ethnic groups. We will also study the microRNA expression profile of the same tumors. MicroRNAs are a class of small noncoding RNAs that are known to control the expression of other genes at the posttranscriptional level. We hypothesize that the mRNA and microRNA expression profiles of African-Americans are associated with an early onset of the disease, a more rapid cancer progression and poor disease outcome. Genes that are differentially expressed between African-American and Caucasian males may have a general significance in prostate cancer progression. Our study design is aimed to establish molecular profiles that distinguish: 1) prostate cancer in African-Americans from prostate cancer in Caucasians, 2) tumor-associated stroma of African-American cancer patients from tumor-associated stroma of Caucasian cancer patients, and 3) high pathological stage from low pathological stage tumors. We will use laser-captured microdissection (LCM) to collect small tissue samples that are highly enriched for either cancer tissue or the surrounding stroma. The microdissected samples will be used to establish the mRNA expression profile of cancer cells and the adjacent stroma. We will also isolate total RNA of whole tissue samples. The total RNA will be used to determine microRNA and mRNA expression. This approach will allow us to study the microRNA expression profile of prostate tumors and to compare how expression changes of microRNA relate to expression changes of mRNA in the same tissue sample.We received 59 frozen, OCT-preserved prostate tumors from the NCI Prostate Tissue Network (CPCTR) for a pilot study to investigate differences in the gene expression of prostate tumors based on the race/ethnic background of the patients. We also received 18 tumors from the University of Maryland. The tumors are from African-American and Caucasian males, and have a similar stage and Gleason score distribution in the two groups. All cases had a diagnosis of adenocarcinoma and did not receive radiation, chemotherapy, hormone therapy, or immunotherapy, prior to the prostatectomy.